5-103136856-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001276277.3(PPIP5K2):c.401+34A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0203 in 1,477,420 control chromosomes in the GnomAD database, including 1,081 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.052 (528 hom., cov: 32)
  • Exomes 𝑓: 0.017 (553 hom.)
• Consequence: PPIP5K2 NM_001276277.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.07

Genes affected

PPIP5K2 (HGNC:29035): (diphosphoinositol pentakisphosphate kinase 2) This gene encodes a member of the histidine acid phosphatase family of proteins. Despite containing a histidine acid phosphatase domain, the encoded protein functions as an inositol pyrophosphate kinase, and is thought to lack phosphatase activity. This kinase activity is the mechanism by which the encoded protein synthesizes high-energy inositol pyrophosphates, which act as signaling molecules that regulate cellular homeostasis and other processes. This gene may be associated with autism spectrum disorder in human patients. [provided by RefSeq, Sep 2016]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.62).
• BP6: Variant 5-103136856-A-G is Benign according to our data. Variant chr5-103136856-A-G is described in ClinVar as [Benign]. Clinvar id is 1261411.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.157 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PPIP5K2	NM_001276277.3	c.401+34A>G		intron_variant		ENST00000358359.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PPIP5K2	ENST00000358359.8	c.401+34A>G		intron_variant		1	NM_001276277.3	P4

Frequencies

GnomAD3 genomes AF: 0.0520 AC: 7911 AN: 152184 Hom.: 526 Cov.: 32

Gnomad AFR AF: 0.160

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0161

Gnomad ASJ AF: 0.00577

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00145

Gnomad FIN AF: 0.00151

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0132

Gnomad OTH AF: 0.0397

GnomAD3 exomes AF: 0.0195 AC: 4883 AN: 250774 Hom.: 245 AF XY: 0.0163 AC XY: 2206 AN XY: 135634

Gnomad AFR exome AF: 0.166

Gnomad AMR exome AF: 0.0106

Gnomad ASJ exome AF: 0.00885

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00111

Gnomad FIN exome AF: 0.00286

Gnomad NFE exome AF: 0.0136

Gnomad OTH exome AF: 0.0160

GnomAD4 exome AF: 0.0166 AC: 22028 AN: 1325118 Hom.: 553 Cov.: 21 AF XY: 0.0155 AC XY: 10324 AN XY: 666722

Gnomad4 AFR exome AF: 0.166

Gnomad4 AMR exome AF: 0.0117

Gnomad4 ASJ exome AF: 0.00743

Gnomad4 EAS exome AF: 0.0000257

Gnomad4 SAS exome AF: 0.00120

Gnomad4 FIN exome AF: 0.00351

Gnomad4 NFE exome AF: 0.0150

Gnomad4 OTH exome AF: 0.0192

GnomAD4 genome AF: 0.0521 AC: 7936 AN: 152302 Hom.: 528 Cov.: 32 AF XY: 0.0495 AC XY: 3684 AN XY: 74490

Gnomad4 AFR AF: 0.160

Gnomad4 AMR AF: 0.0161

Gnomad4 ASJ AF: 0.00577

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00124

Gnomad4 FIN AF: 0.00151

Gnomad4 NFE AF: 0.0132

Gnomad4 OTH AF: 0.0393

Alfa AF: 0.0288 Hom.: 38

Bravo AF: 0.0583

Asia WGS AF: 0.00982 AC: 34 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 22, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
Cadd	Benign	13
Dann	Benign	0.91

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs74429703; hg19: chr5-102472560;